The perinatal period is a critical one in lung development. It is then that the type II pulmonary epithelial cell completes its differentiation and begins to synthesize and secrete pulmonary surfactant. While little is known about factors (i.e., hormonal) which control the differentiation of type II cell function, recent reports indicate that the developing lung is a target organ for thyroid hormones. The objective of this proposal is to determine if the developing type II cell is a major target cell for thyroid hormones. Morphologic and biochemical techniques will be used to determine the parameters of type II cell differentiation affected by thyroid hormones at various times in gestation. In a series of in vivo studies, propylthiouracil (with and without replacement therapy) will be administered to assess potential alterations in either the rate or nature of perinatal type II cell differentiation as a result of altered thyroid hormone environments. These results will be compared to results obtained using a recently developed in vitro system which permits direct examination of an enriched (90%) population of developing type II cells. Such cultures will be used to study the importance of thyroid hormones, as well as their possible synergism with glucocorticoids, in normal type II cell maturation. Finally, the ontogeny of nuclear T3 receptors will be studied in both whole lung and type II cell-rich cultures obtained at critical times during normal lung development. Correlation of the results of the nuclear receptor studies with the determinations of the particular parameters of type II cell differentiation affected by altered hormonal environments will allow us to test our hypothesis that these developing cells are specific target cells for thyroid hormones. If this study indicated that thyroid hormones (alone or in combination with glucocorticoids) are important in the development of the lung, then another mode of prevention and/or therapy of RDS, a condition characterized by lung immaturity, may be possible.